Yamanaka Kazunori, Mizuarai Shinji, Eguchi Tomohiro, Itadani Hiraku, Hirai Hiroshi, Kotani Hidehito
Department of Cancer Research, Banyu Tsukuba Research Institute, Merck Research Laboratory, Tsukuba, Ibaraki 300-2611, Japan.
Genomics. 2009 Oct;94(4):219-27. doi: 10.1016/j.ygeno.2009.06.003. Epub 2009 Jun 25.
CDK inhibitors CDKN1B (p27) and CDKN2A (p16) inhibit cell cycle progression. A lower expression level of only p27 has been correlated with poorer prognosis in various types of clinical cancers. The difference may be the result of distinct genes downstream of these CDK inhibitors. Here, we report that NF-Y transcription factor-targeted genes specifically down-regulated by p27 correlate with poor prognosis in multiple tumor types. We performed mRNA expression profiling in HCT116 cells over-expressing either p16 or p27 and identified their regulatory genes. In silico transcription factor prediction indicated that most of the genes specifically down-regulated by p27 are controlled by NF-Y. Under the hypothesis that NF-Y-targeted genes are responsible for poor prognosis, we predicted prognosis in four types of cancer based on genes with the NF-Y motif, and found a significant association between the expression of NF-Y-targeted genes and poor prognosis.
细胞周期蛋白依赖性激酶（CDK）抑制剂CDKN1B（p27）和CDKN2A（p16）可抑制细胞周期进程。仅p27表达水平较低与多种临床癌症的预后较差相关。这种差异可能是这些CDK抑制剂下游不同基因所致。在此，我们报告p27特异性下调的NF-Y转录因子靶向基因与多种肿瘤类型的预后不良相关。我们在过表达p16或p27的HCT116细胞中进行了mRNA表达谱分析，并鉴定了它们的调控基因。计算机转录因子预测表明，p27特异性下调的大多数基因受NF-Y调控。基于NF-Y靶向基因导致预后不良的假设，我们根据具有NF-Y基序的基因预测了四种癌症类型的预后，发现NF-Y靶向基因的表达与预后不良之间存在显著关联。
